Pseudohypoparathyroidism (PHP) is an autosomal dominant disorder, which is related with parathormone target organ resistance resulting from mutations in guanine nucleotide binding protein (G protein) and alpha stimulating activity polypeptide 1 (GNAS1
G-protein coupled receptor mutation analysis was completed on native liver tissue obtained at transplant which identified one of the typical pathogenic variants (c.602G>A.p.R201H) in exon 8 of the GNAS1
(adenylate cyclase stimulatory G protein) gene that has been associated with the MAS phenotype (1, 2, 3).
In addition, a recent meta-analysis study points to a putative role for GNAS1
mutation as a prognostic factor of treatment response to somatostatin receptor ligands (3).
The molecular etiology has been linked with a mutation in the Gs-[alpha] gene, affecting proliferation and differentiation of fibroblasts/osteoblasts, which is coded by the GNAS1
gene (guanine nucleotide-binding protein, a stimulating activity polypeptide) (1-3).
The human GNAS1
gene is imprinted and encodes distinct paternally and biallelically expressed G proteins.
The etiology of the disorder is a mutation in the GNAS1
gene at chromosome 20q13.2-13.3, which encodes for the alpha-subunit of a stimulatory G protein (1, 3).
MAS is thought to be due to a point mutation of the GNAS1
gene on chromosome 20q13.2 and is characterised by polyostotic fibrous dysplasia, autonomous endocrine hyperfunction, and abnormal skin pigmentation (cafe-au-lait spots) [1, 2].
In addition, a few studies also explored the association between the recurrence risk and polymorphisms, including T393C SNP of Galphas gene (GNAS1
), CD40 (rs745307, rs11569309, and rs3765457), and E33SNP of thyroglobulin (Tg) (Tg E33SNP) in GD patients after ATD withdrawal [41, 42, 69].
Presneau et al., "GNAS1
mutations occur more commonly than previously thought in intramuscular myxoma," Modern Pathology, vol.
Fibrous dysplasia is a developmental tumor like sporadic condition that results from a post zygotic mutation in GNAS1
(Guanine Nucleotidebinding Protein, a stimulating activity polypeptide 1) gene.
Mutations in the [alpha]-stimulating activity polypeptide 1 gene (GNAS1
), which encodes a guanine nucleotide-binding protein, lead to the development of FD (2, 6).
Isolated PTH resistance (PHPIb) can result from mutations within the GNAS1
gene but is more commonly caused by epigenetic imprinting abnormalities affecting the upstream exon 1A (9).